Clinical And Molecular Pathological Features Of Lung Adenocarcinomas/adenosquamous Lung Carcinomas With Regional Lymph Node Metastasis

Objective:To investigate EGFR, ALK, ROS1 and RET gene status in lung adenocarcinomas/ adenosquamous lung carcinomas with regional lymph node metastasis and their common and specific clinicopathological characteristics.Methods:Patients who were confirmed as primary lung adenocarcinomas/adenosquamous lung carcinomas with N1-N2 lymph node metastasis by resected samples were enrolled. ALK, EGFR, ROS1 and RET were identified by amplification refractory mutation system (ARMS) fluorescence quantitative PCR. Clinicopathological characteristics were assessed and the relationship between gene status and clinicopathological features was analyzed.Results:Of 283 patients enrolled, the frequency of the EGFR mutations, and the ALK, ROS1 and RET fusions were 43.1% (122/283),11.0% (31/283),1.8% (5/283) and 3.5% (10/283), respectively. And no mutations (wild type [WT]) in any of the 4 genes (WT/WT/WT/WT) was 42.4%(120/283). Five patients had the coexistence of the EGFR mutation and the ALK rearrangement. ALK, ROS1 and RET were mutually exclusive. EGFR mutation occurred at a significantly higher frequency in patients with female or well differentiation (all P<0.05). Young age (≤ 60 years old), poor differentiation and EGFR negative patients had significant greater ALK mutation frequencies than old age (>60 years old), well differentiation and EGFR mutation patients, respectively (all P<0.05). ROS1 fusion frequency was significantly higher among patients with poor differentiation (P=0.005). Age, sex, smoking history, tumor size, TNM stage, N stage and tumor marker didn’t correlate with RET alteration (all P>0.05). The significance existed between the differentiation of EGFR and ALK group (P=0.001).Conclusion:Among the cohort with lung adenocarcinomas/adenosquamous lung carcinomas with regional lymph node invasion, ALK rearrangement frequency was higher. Coexistence of ALK and EGFR occurred while ALK, ROS1 and RET were mutually exclusive. EGFR, ALK, ROS1 and RET occurred with various distinct and common clinicopathological characteristics.